ArticleNeuropharmacology2002
Progesterone withdrawal increases the alpha4 subunit of the GABA(A) receptor in male rats in association with anxiety and altered pharmacology - a comparison with female rats.
Article in Neuropharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 105 citations in OpenAlex.
- Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial.Translational psychiatry · 2022Trial
- Regulatory Mechanisms and Safety Evaluation of Exogenous Progesterone for Suppression of Rutting Behavior in Male Sika Deer (Animals : an open access journal from MDPI · 2026Article
- Shuyu capsule improves estrous cycle-dependent depression-like behavior in premenstrual dysphoric disorder (PMDD) mice by increasing GABAergic neuronal activation and downregulating GABAJournal of Zhejiang University. Science. B · 2025Article
- Transcription of GABATranslational psychiatry · 2025Article
- Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior.Biomolecules · 2023Article
- Neurosteroid enantiomers as potentially novel neurotherapeutics.Neuroscience and biobehavioral reviews · 2023Review
- The impact of the ovarian cycle on anxiety, allopregnanolone, and corticotropin releasing hormone changes after motherhood in female rats and women.Translational psychiatry · 2023Article
- Long-Term Management of Generalised Anxiety Disorder with Low-Dose Continuous Infusions of Flumazenil: A Case Series.Behavioral sciences (Basel, Switzerland) · 2022Article
- Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats.International journal of molecular sciences · 2022Article
- The Specificities of Elite Female Athletes: A Multidisciplinary Approach.Life (Basel, Switzerland) · 2021Review
- A forced swim-based rat model of premenstrual depression: effects of hormonal changes and drug intervention.Aging · 2020Article
- Progesterone, reproduction, and psychiatric illness.Best practice & research. Clinical obstetrics & gynaecology · 2020Review
- Paeonol at Certain Doses Alleviates Aggressive and Anxiety-Like Behaviours in Two Premenstrual Dysphoric Disorder Rat Models.Frontiers in psychiatry · 2020Article
- Allopregnanolone-based treatments for postpartum depression: Why/how do they work?Neurobiology of stress · 2019Article
- GABAJournal of neurophysiology · 2019Article
- Transcriptomic Analysis Reveals Sex-Dependent Expression Patterns in the Basolateral Amygdala of Dominant and Subordinate Animals After Acute Social Conflict.Molecular neurobiology · 2019Article
- Short-term sleep fragmentation enhances anxiety-related behavior: The role of hormonal alterations.PloS one · 2019Article
- Histone deacetylases mediate GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation.Frontiers in physiology · 2018Review
- BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia.Psychoneuroendocrinology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Withdrawal from the neurosteroid 3alpha,5alpha-allopregnanolone after chronic administration of progesterone increases anxiety in female rats and up-regulates the alpha4 subunit of the GABA(A) receptor (GABA(A)-R) in the hippocampus. We investigated if these phenomena would also occur in male rats. Progesterone withdrawal (PWD) induced higher alpha4 subunit expression in the hippocampus of both male and female rats, in association with increased anxiety (assessed in the elevated plus maze) comparable to effects previously reported. Because alpha4-containing GABA(A)-R are insensitive to the benzodiazepine (BDZ) lorazepam (LZM), and are positively modulated by flumazenil (FLU, a BDZ antagonist), we therefore tested the effects of these compounds following PWD. Using whole-cell patch clamp techniques, LZM-potentiation of GABA ((EC20))-gated current was markedly reduced in CA1 pyramidal cells of male rats undergoing PWD compared to controls, whereas FLU had no effect on GABA-gated current in control animals but increased it in PWD animals. Behaviorally, both male and female rats were significantly less sensitive to the anxiolytic effects of LZM. In contrast, FLU demonstrated significant anxiolytic effects following PWD. These data suggest that neurosteroid regulation of the alpha4 GABA(A)-R subunit may be a relevant mechanism underlying anxiety disorders, and that this phenomenon is not sex-specific.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.